POS0489 CCL24 SERUM CONCENTRATION CORRELATES WITH DISEASE ACTIVITY AND WORSE PROGNOSIS IN DIFFUSE CUTANEOUS SSc: A PROMISING BIOLOGICAL TARGET TO PREVENT DISEASE PROGRESSION
Authors: M. Segal Salto, A. Mor, F. Del Galdo
Journal: Annals of the Rheumatic Diseases (2022)

Background Linking novel therapeutic targets for diffuse cutaneous Systemic Sclerosis (dcSSc) to markers of disease severity and clinical outcome will enable directing the right therapeutic agents to the appropriate patient populations. Such correlation will also support patient stratification in clinical trials, increasing their informative value and success rates. CCL24 is a chemokine within the Eotaxin family, that has been shown to have a dual pro-inflammatory and pro-fibrotic role in SSc. CCL24 and its receptor, CCR3, were found to be over-expressed in SSc skin and serum samples. In-vivo CCL24 blockage was associated with reduction of bleomycin induced skin and lung injury. Objectives We aimed to study the role of CCL24 in dcSSc using patient cohorts, by correlating its serum levels to disease activity markers and disease progression. Methods Retrospective and longitudinal dSSc patients’ cohorts were analyzed for CCL24 circulating levels, clinical measurement and disease related bio-markers. Results In a retrospective cohort of 56 dcSSC patients, CCL24 serum levels were significantly higher in patients that had positive anti topoisomerase antibody (ATA) compared to patients with negative ATA. In addition, within the ATA positive patients, ones that had high serum CCL24 levels (≥1500 pg/ml) also presented significantly higher fibrotic activity reflected by a higher enhanced liver fibrosis (ELF) score compared to ATA positive patients with low CCL24 (&lt;1500 pg/ml). In a second longitudinal cohort of 66 patient, baseline CCL24 levels positively correlated with ELF score (r=0.42, p≤0.0005). Patients with high baseline CCL24 serum levels were also more likely to experience lung disease progression, measured by reduction in forced vital capacity (FVC) during 12 months(7 out of 17 patients with CCL24 ≥ 1500 pg/ml had at least -5% reduction of FVC). Consistent with these data, patients with normal FVC at baseline (&gt;80% predicted) which experienced worsening in the next 12 months (at least 7%) had a statistically significant higher baseline serum CCL24 (Average 2,275 pg/ml) compared to patients that had no worsening in FVC over time (average 962 pg/ml, p≤0.001). Interestingly, the same group showed an even steeper reduction in DLCO % predicted (-6.8% vs -0.2%, p≤0.05). Conclusion We show here using two dcSSc patient cohorts, that CCL24 serum levels are correlated with disease activity and worse prognosis reflected by high fibrotic activity and deterioration of lung function over time. This reverse translational study supports the role of CCL24 as a therapeutic target for dcSSc and it has informed a phase 2 study testing CM-101, a CCL24 neutralizing antibody, in dcSSc patients to be started in 2022. Disclosure of Interests Michal Segal Salto Employee of: Chemomab Therapeutic Ltd., Adi Mor Employee of: Chemomab Therapeutics Ltd., Francesco Del Galdo Consultant of: Chemomab Therapeutic Ltd., Grant/research support from: Chemomab Therapeutic Ltd.